Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment

Environmental Toxicology and Chemistry - Tập 34 Số 12 - Trang 2782-2790 - 2015
Justin C. Lo1, Gayatri N. Allard2, S. Victoria Otton2, David A. Campbell3, Frank A. P. C. Gobas1,2
1Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
2School of Resource and Environmental Management, Simon Fraser University, Burnaby, British Columbia, Canada
3Department of Statistics and Actuarial Science, Simon Fraser University, Surrey, British Columbia, Canada

Tóm tắt

AbstractIn vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9‐methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first‐order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis–Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin‐film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery–based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery–based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances. Environ Toxicol Chem 2015;34:2782–2790. © 2015 SETAC

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Thông tin xuất bản

Environmental Toxicology and Chemistry

Tập 34 Số 12

2782-2790

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